Chemoprotective effects of inositol hexaphosphate against cyclophosphamide-induced testicular damage in rats

Maha I Alkhalaf,Areej A Eskandrani,Nouf A Babteen,Wafa S Alansari,Afnan M Alnajeebi,Fawzia A Alshubaily,Manal A Tashkandi

doi:10.1038/s41598-020-68608-9

Maha I Alkhalaf, Areej A Eskandrani + Show 5 more

Open Access

https://doi.org/10.1038/s41598-020-68608-9

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Abstract

Cyclophosphamide (CP) is commonly used as an anticancer agent but has been associated with high toxicity in several animal organs, including the testes. Inositol hexaphosphate (IP6) is a polyphosphorylated carbohydrate that is present in foods with high fibre contents and has a wide range of essential physiological and pathological activities. Thus, we estimated the defensive effects of IP6 against CP-related testicular toxicity in rats. Sperm counts, motilities, viabilities and abnormalities and levels of testosterone, luteinising hormone and follicle-stimulating hormone were evaluated. Testicle specimens were also processed for histological and biochemical analyses, including determinations of malondialdehyde, nitric oxide, total antioxidant capacity, alkaline phosphatase, acid phosphatase, gamma glutamyl transferase, ß-glucuronidase, c-reactive protein, monocyte chemoattractant protein and leukotriene-4 and in comet assays. CP treatments were associated with deleterious histopathological, biochemical and genetic changes in rat testicles, and these were ameliorated by IP6 supplements in drinking water.

Highlights

Cyclophosphamide (CP) is commonly used as an anticancer agent but has been associated with high toxicity in several animal organs, including the testes
CP-induced testicular injury is indicated by significant reductions (p < 0.05) in sperm counts, sperm viabilities and sperm motilities and by significant increases (p < 0.05) in sperm abnormalities, as compared with the healthy control group
Especially alkylating agents, are genotoxic and are associated with reproductive toxicity pending on their antineoplastic activities, overall dosages, durations of treatment and individual s ensitivities[23] Because of their high mitotic activity, spermatogenic cells are targeted by these alkylating agents

Summary

Introduction

Cyclophosphamide (CP) is commonly used as an anticancer agent but has been associated with high toxicity in several animal organs, including the testes. Following hepatic metabolic activation, CP is converted to 4-hydroxy Cyclophosphamide, which transforms into the cytotoxic metabolites acrolein and phosphoramide mustard. These cytotoxic metabolites form covalent bonds with DNA and proteins and thereby contribute to cell death following enzyme activation[6]. The anti-cancer effects of CP are correlated with phosphoramide mustard production, acrolein is correlated with toxic side effects. These negative biochemical responses lead to oxidative stress and reduced fertility in patients. Several medical plants reportedly mitigate the harmful effects of CP on certain reproductive parameters in r ats[13]

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